Calcium signaling via voltage‐dependent L‐type Ca2+ channels

AbstractIn excitable cells such as muscles and neurons, the voltage‐dependent L‐type Ca2+ channel is one of the most important pathways for Ca2+ influx from extracellular space in response to the cell membrane depolarization. Ca2+ ion through this channel works as a Ca2+ signal that regulates fast (on time scale of milliseconds; e.g. muscle contraction) and long‐term (on a time scale of days or weeks; e.g. gene expression) cellular responses. Many important signal molecules are activated via Ca2+ signal, such as Ca2+‐dependent protease (calpain), calcium/calmodulin dependent kinases (CaMKs), phosphatase (calcineurin), and mitogen‐activated protein kinases (MAPKs). They are activated by temporally and spatially restricted Ca2+ signals, thus strictly regulated in native tissues. Many kinds of Ca2+ channels are involved in the rise of the intracellular Ca2+ concentration. They are not mere routes of Ca2+ influx but also machineries that decide which specific signal cascade should be activated. Recently, the molecular mechanisms by which Ca2+ influx through L‐type Ca2+ channels can activate specific signal cascades have been clarified. In this review, we describe the role of Ca2+ signaling via L‐type Ca2+ channels particularly in cardiac myocytes and neurons with emphasis on the mechanisms underlying the activation of the specific Ca2+ signals by the L‐type Ca2+ channel machinery.